| Summary: | <p>Living matter describes systems which convert chemical energy from their surroundings to grow or to generate active forces. Biological tissues are composed of many anisotropic and active cells, which can exhibit nematic long-range orientational order. The continuous injection of energy on the single-cell level can lead to complex flow patterns on the tissue scale and topological defects in the cell orientation field. This thesis explores different applications of active nematic theories to living systems. By including key biological features in active hydrodynamic models, we investigate the interplay between collective flows, shape formation and topological defects in two- and three-dimensional tissues.</p>
<p>Using continuum simulations, we investigate the morphology of active, self-deforming cell aggregates, where cell-generated active stress drives flows which can deform the surface. The resulting shape dynamics, such as the formation of finger-like protrusions, surface wrinkles or invagination, are reminiscent of many biological processes, ranging from morphogenesis to collective cancer invasion. We explore how spatial variations of active stress affect the dynamics in active nematic systems. We find that activity gradients induce forces which cause cell orientations and topological defects to preferentially align along a particular direction. Based on these results, we subsequently investigate multicellular spheroids, which are spherical cell clusters widely used as model systems for studying tumor dynamics. The competition over limited resources within spheroids generates proliferation gradients, leading to radial cell flows and activity gradients, both of which can affect the orientation axis of cells. As a result, distinct cell alignment patterns emerge within aggregates, which allows us to infer dynamical tissue parameters for different cell types based on experimental measurements of cell orientations inside spheroids. Finally, we motivate a continuum model for two-dimensional tissues, in which the direction of active stress is decoupled from the orientation axis of cell shape. We show that misalignment between active forces and cell shapes in tissues is linked to topological defects in the cell orientation field, both in simulations and experiments. This suggests that the direction of active stress can vary continuously within tissues, which challenges the underlying assumptions of some widely used tissue models.</p>
<p>This thesis demonstrates how physical continuum models of active materials can help us to understand shape formation and collective cell organisation in living matter.</p>
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